Asthma is etiologically and clinically heterogeneous, making the genomic basis of
asthma difficult to identify. We exploited the strain-dependence of a murine model of allergic airway disease to identify different genomic responses in the lung. BALB/cJ and C57BL/6J mice were sensitized with the immunodominant
allergen from the Dermatophagoides pteronyssinus species of house dust mite (
Der p 1), without exogenous adjuvant, and the mice then underwent a single challenge with
Der p 1. Allergic
inflammation, serum antibody titers, mucous
metaplasia, and
airway hyperresponsiveness were evaluated 72 hours after airway challenge. Whole-lung gene expression analyses were conducted to identify genomic responses to
allergen challenge. Der p 1-challenged BALB/cJ mice produced all the key features of allergic airway disease. In comparison, C57BL/6J mice produced exaggerated Th2-biased responses and
inflammation, but exhibited an unexpected decrease in
airway hyperresponsiveness compared with control mice. Lung gene expression analysis revealed genes that were shared by both strains and a set of down-regulated genes unique to C57BL/6J mice, including several
G-protein-coupled receptors involved in airway smooth muscle contraction, most notably the
M2 muscarinic receptor, which we show is expressed in airway smooth muscle and was decreased at the
protein level after challenge with
Der p 1. Murine strain-dependent genomic responses in the lung offer insights into the different
biological pathways that develop after
allergen challenge. This study of two different murine strains demonstrates that
inflammation and
airway hyperresponsiveness can be decoupled, and suggests that the down-modulation of expression of
G-protein-coupled receptors involved in regulating airway smooth muscle contraction may contribute to this dissociation.